2020 Fiscal Year Final Research Report
Cardiac lipid droplets and gap junction remodeling
| Project/Area Number |
18K08471
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | University of Fukui |
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Principal Investigator |
Suzuki Jinya 福井大学, 学術研究院医学系部門(附属病院部), 講師 (20293417)
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| Co-Investigator(Kenkyū-buntansha) |
弘瀬 雅教 岩手医科大学, 薬学部, 教授 (40273081)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 脂肪心筋 / 脂肪滴 / Perilipin 2 / 心房細動 / Connexin 43 / 脂肪毒性 |
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| Outline of Final Research Achievements |
We have created a mouse model of cardiac steatosis: cardiac-specific PLIN2-overexpressing mice (PLIN2-Tg). PLIN2-Tg are prone to atrial fibrillation (AF) associated with lateral distribution of a gap junction protein connenxin (Cx)43 in atrial cardiomyocytes. Analysis of aged PLIN2-Tg have revealed that accumulation of ceramide, diacylglycerol and triacylglycerol (TAG), and altered phospholipid profile might be critical for Cx43 remodeling in the aged condition. Eight week-administration of a GLP-1 agonist dulaglutide achieved 60% decrease in atrial TAG content, 45% decrease in AF susceptibility, and 60% decrease in AF duration. Cardiac steatosis would be a novel therapeutic target for AF in diabetic patients.
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| Free Research Field |
脂質代謝
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病患者は心房細動などの不整脈を合併し易く、それらが患者の健康寿命に多大な影響を与えている。本研究は糖尿病性心筋症の特徴である脂肪心筋が心房細動を誘発する分子メカニズムの一端を解明し、その治療法を検証した。GLP-1受容体アゴニストは既に糖尿病治療薬として使われているため、即座に臨床応用が可能である。本研究により「脂肪滴→刺激伝導障害」という新たな病態生理が解明され、糖尿病患者の不整脈に対する新たな治療戦略へ発展すると思われる。
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